Methods for improving neural communication between tissue regions

ABSTRACT

Described are methods for the improvement of neural communication between implanted and existing tissue. Methods herein use synchronous low frequency magnetic or electric stimulation of both regions to enhance communication and facilitate regeneration of nerve fibers across the tissue interface.

CROSS REFERENCE TO A RELATED APPLICATION

This application is a continuation application of U.S. application Ser.No. 15/226,578, filed Aug. 2, 2016, the disclosure of which isincorporated herein by reference in its entirety, including any figures,tables, and drawings.

BACKGROUND OF THE INVENTION

Tissue implantation or grafting is a common surgical procedure in whichtissue is transplanted from one area to another on a person's body, orfrom another person, without bringing its own blood supply. This is incontrast to flap surgery, in which the grafted tissue has an intactblood supply. The implanted tissue may be engineered, such as from stemcells and a collagenous scaffold. One important type of tissueengineering involves the formation of neural tissue, which is implantedto promote nerve regeneration and to repair damaged nerves. It is alsopossible to create implanted tissue via intravenous stem cellinjections, through natural concentration of stem cells in affectedregions.

Neural communication is required between the implanted tissue andexisting tissue in order to allow sensory and functional information tobe passed between the host tissue and implanted tissue. The implantedtissue generally contains nerve fibers that provide sensory orfunctional communication between the implanted tissue and the host. Inmany cases following the implantation procedure, however, neuralcommunication between the implanted tissue and the existing tissue islimited or nonexistent, even though the implanted tissue is viable witha reasonable blood supply.

Currently, procedures used to improve neural communication withimplanted tissue include peripheral nerve reconstruction, in whichnerves are cut and re-approximated using very small sutures. Anotheroption is bio-artificial nerve guidance conduits in order to guideaxonal regrowth and connectivity. However, surgical procedures such asthese are time consuming, highly invasive, and involve a long recoveryperiod for the patient. It is apparent that a non-invasive approachwould have significant benefits over existing technology.

SUMMARY

Magnetic stimulation utilizes a pulsed magnetic field applied to aregion near a target area. The magnetic pulses affect neuronal firing inthe target area, either directly through active depolarization with ahigh power magnetic field, or indirectly through entrainment and fieldeffect with a low power magnetic field. It has been shown that lowfrequency (<30 Hz) magnetic pulses enhance communication through nervesin the target area. A magnetic field generates an induced electric fieldin the neurons and surrounding tissue. The electric field from themagnetic pulses has an entrainment effect on neurons in the area,encouraging synchronous firing between nearby neurons.

By providing synchronous magnetic pulses to implanted tissue andexisting tissue, it is possible to improve communication between thetwo, resulting in better passing of sensory information and functionalcontrol between the brain and implanted tissue. In addition, synchronousstimulation encourages the regeneration of nerve fibers across theinterface between the two regions of tissue. Improved communication canoccur via, for example, improved communication between existing nerves,by growth of new nerves, and/or via regeneration of nerves, includingaxonal growth into nerve grafts and/or into the distal end of severednerves.

In one aspect, the subject invention provides methods of improvingneural communication through the interface between a first distinctregion of tissue and a second distinct region of tissue in the body of aperson, wherein the method comprises administering repetitive magneticfield pulses synchronously to both regions of tissue.

Due to the spreading of the magnetic field, it may be that a singlemagnetic field source affects both implanted and existing tissue.However, two or more separate magnetic field sources may be used toensure implanted and existing tissue are properly targeted.

Thus, in some embodiments of at least one aspect described above, themagnetic pulses administered to the first region of tissue and thesecond region of tissue are generated by a single magnetic field source.In some embodiments of at least one aspect described above, the magneticpulses administered to the first region of tissue and the second regionof tissue are generated by more than one magnetic field source.

Preferably the magnetic pulses are generated using an electromagnet, butother methods may also be used. In some embodiments of at least oneaspect described above, the magnetic pulses are generated by a coil or amoving permanent magnet.

When low frequency magnetic pulses are applied, neural communicationwithin tissue and between tissues is improved. Preferably, the frequencyof magnetic pulses is fixed at or near a target frequency, but it mayalso vary within a range, which may result in improved efficacy. In someembodiments of at least one aspect described above, the magnetic pulsefrequency is fixed at or near a target frequency. In some embodiments ofat least one aspect described above, the magnetic pulse frequency hopsperiodically about an average target frequency. This hopping may berandom or may be in a fixed pattern. In some embodiments of at least oneaspect described above, the magnetic pulse frequency hops periodicallybetween random values within a range about the average target frequency.In some embodiments of at least one aspect described above, the magneticpulse frequency hops periodically in a specific pattern about theaverage target frequency.

The frequency of magnetic pulses should be low in order to improveneural communication. In some embodiments of at least one aspectdescribed above, the magnetic pulse target frequency is from about 1 Hzto about 10 Hz. In some embodiments of at least one aspect describedabove, the magnetic pulse target frequency is from about 10 Hz to about30 Hz.

Because much of the method of action for improved communication can beachieved through entrainment, it is not necessary that stimulation besuper-threshold, able to actively depolarize neurons. Instead, themagnetic field strength can be set over a wide range. In someembodiments of at least one aspect described above, the strength of themagnetic pulses is from about 10 Gauss to about 4 Tesla. In general,however, the effect may be improved if the strength of the magneticfield at the target location is strengthened, up to the point wherestimulation is bothersome or painful to the patient. In some embodimentsof at least one aspect described above, the strength of the magneticpulses is adjusted based on the tolerance of the patient.

Magnetic pulses induce an electric current or electric voltage potentialin or near nerves in the implanted tissue and existing tissue.Therefore, in addition to magnetic stimulation, it is also possible toachieve similar benefits through direct electrical stimulation, eithertranscutaneously with electrodes placed on the skin above the targetregion, or subcutaneously, using, for example, needle-electrodes, or animplanted electrode array. In one aspect are methods of improving neuralcommunication between a first region of tissue and a second region oftissue in the body of a person comprising administering alternatingelectric currents synchronously to both regions of tissue.

The synchronous alternating electric currents in the two regions may begenerated by a single source, where electric current flows through theinterface between the two regions, or by multiple sources, where eachregion contains its own electric current source. In some embodiments ofat least one aspect described above, the electric currents administeredto the first region of tissue and the second region of tissue aregenerated by a single electric current source where the current travelsacross the interface between the regions. In some embodiments of atleast one aspect described above, the electric currents administered tothe first region of tissue and the second region of tissue are generatedby more than one electric current source that stimulates the two regionsconcurrently.

When low frequency electric currents are applied to regions of tissue,neural communication within a tissue and between tissues is improved.Preferably, the frequency of electric currents is fixed at or near atarget frequency, but it may also vary within a range, which may resultin improved efficacy. In some embodiments of at least one aspectdescribed above, the electric current frequency is fixed at or near atarget frequency. In some embodiments of at least one aspect describedabove, the electric current frequency hops periodically about an averagetarget frequency. This hopping may be random or may be in a fixedpattern. In some embodiments of at least one aspect described above, theelectric current frequency hops periodically between random valueswithin a range about the average target frequency. In some embodimentsof at least one aspect described above, the electric frequency hopsperiodically in a specific pattern about the average target frequency.

The frequency of electric current should be low in order to improveneural communication. In some embodiments of at least one aspectdescribed above, the electric current target frequency is from about 1Hz to about 10 Hz. In some embodiments of at least one aspect describedabove, the electric current target frequency is from about 10 Hz toabout 30 Hz.

The regions of tissue may be endogenous or engineered. For example, intissue grafting or in a tissue flap, both regions may be endogenous.Engineered tissue may be generated using stem cells or anothertechnique, or may be transplanted from another region of the body orfrom a donor. Engineered tissue may also result from stem cellinjections, either directly to the treatment site or intravenously, orby stem cell implantation. In some embodiments of at least one aspectdescribed above, the first region of tissue is engineered and the secondregion of tissue is endogenous. In some embodiments of at least oneaspect described above, the first region of tissue is transplanted andthe second region of tissue is endogenous. In some embodiments of atleast one aspect described above, the first region of tissue isgenerated from stem cell injections and the second region of tissue isendogenous.

The type of tissue may vary because tissue implantation can be used toimprove functionality in a variety of organs in the body. In someembodiments of at least one aspect described above, the first or secondregion of tissue comprises muscle tissue. In some embodiments of atleast one aspect described above, the first or second region of tissuecomprises brain tissue. In some embodiments of at least one aspectdescribed above, the first or second region of tissue comprises skintissue. Other embodiments include nerve tissue including (nerve grafts),pancreas, gastrointestinal, kidney, urogenital, and bone tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the features and advantages of the systems andmethods provided will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments and theaccompanying drawings of which:

FIG. 1 shows an exemplary method in which a magnetic field is generatedusing a single coil, where the magnetic field provides synchronousmagnetic stimulation to two distinct regions of tissue.

FIG. 2 shows an exemplary method in which a single coil is placed over aregion of implanted tissue, so that the synchronous magnetic fieldextends to both the implanted tissue and the existing tissue.

FIG. 3 shows an exemplary method in which three coils are placed so thatthey synchronously stimulate a region of implanted tissue as well as theexisting tissue on either side.

DETAILED DESCRIPTION

While certain embodiments have been provided and described herein, itwill be readily apparent to those skilled in the art that suchembodiments are provided by way of example only. It should be understoodthat various alternatives to the embodiments described herein may beemployed, and are part of the invention described herein.

Described herein are methods for novel, effective improvement of neuralcommunication between two distinct regions of tissue. In someembodiments, described are methods that use repetitive magneticstimulation (rMS) to stimulate the two regions synchronously, whichimproves communication and may facilitate nerve regeneration in thetargeted region. It has been shown that low frequency magnetic fieldstimulation enhances communication of nerves in a single targetedregion; however, it is also possible to apply synchronous magneticstimulation to two distinct regions of tissue to improve communicationbetween the two regions.

Improved communication can occur via, for example, improvedcommunication between existing nerves, by growth of new nerves, and/orvia regeneration of nerves, including axonal growth into nerve graftsand/or into the distal end of severed nerves.

The term “target region,” when referring to rMS treatment, is a regionwhere magnetic stimulation is applied, and may encompass one or tworegions of tissue.

The term “region of tissue,” when referring to rMS treatment, is aregion of tissue with a boundary between it and another region oftissue. The tissue may be endogenous, already existing in the body,engineered, such as with stem cells, or transplanted, either from adifferent region of the body or from a donor.

Described herein are methods that improve neural communication throughthe interface between two distinct regions of tissue using synchronouslow frequency stimulation to both regions. These methods involve nomedication, although medication may be administered in conjunction withthe treatment without necessarily altering the effects of the treatment.

Implanted tissue is often used to repair and improve the function ofexisting damaged tissue. Implanted tissue may be endogenous, engineered,or donated. Tissue may also form through the concentration of injectedstem cells. Often, implanted tissue contains nerve cells that areintended to provide sensory or functional information to or from theimplanted tissue. It may be the case that the implanted tissue does nothave effective neural communication with adjacent existing tissuethrough the interface between the two, even though the implanted tissueis viable through the existing blood supply.

When a signal is transmitted through a nerve fiber, a minimum transittime is generally required, which is about 50 milliseconds. This meansthat the highest frequency at which the nerve can fire is about 20 Hz(20 times per second). Magnetic pulses or alternating electric currentadministered to a target location on the nerve cause a voltage potentialin the nerve fibers, and if the magnetic pulses or electric current havea low frequency (less than 30 Hz), then communication in the nerve fiberbecomes enhanced. It has been shown that low frequency stimulation,either electrically or with pulsed magnetic fields, improves neuralcommunication in undamaged tissue. However, in accordance with thesubject invention it is also the case that low frequency electrical ormagnetic stimulation also improves communication across the boundarybetween two distinct tissue regions, such as between implanted tissueand existing tissue, when the stimulation is provided synchronously toboth tissues on either side of the boundary. If the implanted tissue isformed using stem cells, synchronous low frequency stimulation allowsfor the formation of nerve fibers across the tissue boundary.

In one aspect are methods of improving neural communication through theinterface between a first distinct region of tissue and a seconddistinct region of tissue in the body of a subject comprisingadministering repetitive magnetic field pulses synchronously to bothregions of tissue. Due to the spreading of the magnetic field, it may bethat a single magnetic field source affects both the implanted andexisting tissue; however, two or more separate magnetic field sourcesmay be used to ensure implanted and existing tissue is properlytargeted. In some embodiments of at least one aspect of the subjectinvention, the magnetic pulses administered to the first region oftissue and the second region of tissue are generated by a singlemagnetic field source. In some embodiments of at least one aspect of thesubject invention, the magnetic pulses administered to the first regionof tissue and the second region of tissue are generated by more than onemagnetic field source.

Preferably the magnetic pulses are generated using an electromagnet, butother methods may also be used. In some embodiments of at least oneaspect described above, the magnetic pulses are generated by a coil or amoving permanent magnet.

When magnetic pulses are applied that are low frequency, neuralcommunication within tissue and between tissues is improved. Preferably,the frequency of magnetic pulses is fixed at or near a target frequency,but it may also vary within a range, which may result in improvedefficacy. In some embodiments of at least one aspect described above,the magnetic pulse frequency is fixed at or near a target frequency. Insome embodiments of at least one aspect described above, the magneticpulse frequency hops periodically about an average target frequency.This hopping may be random or may be in a fixed pattern. In someembodiments of at least one aspect described above, the magnetic pulsefrequency hops periodically between random values within a range aboutthe average target frequency. In some embodiments of at least one aspectdescribed above, the magnetic pulse frequency hops periodically in aspecific pattern about the average target frequency.

The frequency of magnetic pulses should be low in order to improveneural communication. In some embodiments of at least one aspectdescribed above, the magnetic pulse target frequency is from about 1 Hzto about 10 Hz. In some embodiments of at least one aspect describedabove, the magnetic pulse target frequency is from about 10 Hz to about30 Hz.

Because much of the method of action for improved communication can beachieved through entrainment, it is not necessary that stimulation besuper-threshold, able to actively depolarize neurons. Instead, themagnetic field strength can be set over a wide range. In someembodiments of at least one aspect described above, the strength of themagnetic pulses is from about 10 Gauss to about 4 Tesla. In general,however, the effect may be improved if the strength of the magneticfield at the target location is strengthened, up to the point wherestimulation is bothersome or painful to the patient. In some embodimentsof at least one aspect described above, the strength of the magneticpulses is adjusted based on the tolerance of the patient.

Magnetic pulses induce an electric current or electric voltage potentialin or near nerves in the implanted tissue and existing tissue.Therefore, in addition to magnetic stimulation, it is also possible toachieve similar benefits through direct electrical stimulation, eithertranscutaneously with electrodes placed on the skin above the targetregion, or subcutaneously, possibly using needle-electrodes, or animplanted electrode array. In one aspect are methods of improving neuralcommunication between a first region of tissue and a second region oftissue in the body of a person comprising administering repetitiveelectrical current pulses synchronously to both regions of tissue.

The synchronous alternating electric currents in the two regions may begenerated by a single source, where electric current flows through theinterface between the two regions, or by multiple sources, where eachregion contains its own electric current source. In some embodiments ofat least one aspect described above, the electric currents administeredto the first region of tissue and the second region of tissue aregenerated by a single electric current source, where current flowsthrough the interface between the regions. In some embodiments of atleast one aspect described above, the electric currents administered tothe first region of tissue and the second region of tissue are generatedby more than one electric current source that stimulates the two regionsconcurrently.

When low frequency electric currents are applied to regions of tissue,neural communication within tissue and between tissues is improved.Preferably, the frequency of electric currents is fixed at or near atarget frequency, but it may also vary within a range, which may resultin improved efficacy. In some embodiments of at least one aspectdescribed above, the electric current frequency is fixed at or near atarget frequency. In some embodiments of at least one aspect describedabove, the electric current frequency hops periodically about an averagetarget frequency. This hopping may be random or may be in a fixedpattern. In some embodiments of at least one aspect described above, theelectric current frequency hops periodically between random valueswithin a range about the average target frequency. In some embodimentsof at least one aspect described above, the electric frequency hopsperiodically in a specific pattern about the average target frequency.

The frequency of electric current should be low in order to improveneural communication. In some embodiments of at least one aspectdescribed above, the electric current target frequency is from about 1Hz to about 10 Hz. In some embodiments of at least one aspect describedabove, the electric current target frequency is from about 10 Hz toabout 30 Hz.

The regions of tissue may be endogenous or engineered. For example, intissue grafting or in a tissue flap, both regions may be endogenous.Engineered tissue may be generated using stem cells or anothertechnique, or may be transplanted from another region of the body orfrom a donor. Engineered tissue may also result from stem cellinjections or stem cell implantation. In some embodiments of at leastone aspect described above, the first region of tissue is engineered andthe second region of tissue is endogenous. In some embodiments of atleast one aspect described above, the first region of tissue istransplanted and the second region of tissue is endogenous. In someembodiments of at least one aspect described above, the first region oftissue is generated from stem cell injections and the second region oftissue is endogenous.

The type of tissue may vary because tissue implantation can be used toimprove functionality in a variety of organs in the body. In someembodiments of at least one aspect described above, the first or secondregion of tissue comprises muscle tissue. In some embodiments of atleast one aspect described above, the first or second region of tissuecomprises brain tissue. In some embodiments of at least one aspectdescribed above, the first or second region of tissue comprises skintissue. Other embodiments include nerve tissue (including nerve grafts),pancreas, gastrointestinal, kidney, urogenital, and bone tissue.

FIG. 1 shows an exemplary method in which a synchronous low frequencypulsed magnetic field is generated by a coil (101), which is placed nearthe interface (106) of two distinct regions of tissue (102, 103). Thenerve fibers in the two tissue regions (104, 105) are not directlyconnected across the interface, but the synchronous magnetic fieldfacilitates communication between the disconnected fibers, and thepotential regeneration of new nerve fibers across the interface.

FIG. 2 shows an exemplary method in which a coil (101) generates amagnetic field above a region of implanted tissue (102). The magneticfield extends to affect both the implanted tissue and existing tissue(103) in the target region.

FIG. 3 shows an exemplary method in which multiple coils are used toprovide synchronous magnetic stimulation to implanted and existingtissue. In this method, a central coil (102) is placed so that thehighest energy magnetic field possible is delivered to the implantedtissue (104), while the two side coils (101, 103) are placed to deliverthe highest energy magnetic field possible to the region of existingtissue (105) surrounding the implanted tissue.

Unless the context clearly requires otherwise, throughout thedescription and the claims, the words “comprise,” “comprising,” and thelike are to be construed in an inclusive sense as opposed to anexclusive or exhaustive sense; that is to say, in a sense of “including,but not limited to.” Words using the singular or plural number alsoinclude the plural or singular number respectively. Additionally, thewords “herein,” “hereunder,” “above,” “below,” and words of similarimport refer to this application as a whole and not to any particularportions of this application. When the word “or” is used in reference toa list of two or more items, that word covers all of the followinginterpretations of the word: any of the items in the list, all of theitems in the list and any combination of the items in the list.

The above descriptions of illustrated embodiments of the system,methods, or devices are not intended to be exhaustive or to be limitedto the precise form disclosed. While specific embodiments of, andexamples for, the system, methods, or devices are described herein forillustrative purposes, various equivalent modifications are possiblewithin the scope of the system, methods, or devices, as those skilled inthe relevant art will recognize. The teachings of the system, methods,or devices provided herein can be applied to other processing systems,methods, or devices, not only for the systems, methods, or devicesdescribed.

The elements and acts of the various embodiments described can becombined to provide further embodiments. These and other changes can bemade to the system in light of the above detailed description.

In general, in the following claims, the terms used should not beconstrued to limit the system, methods, or devices to the specificembodiments disclosed in the specification and the claims, but should beconstrued to include all processing systems that operate under theclaims. Accordingly, the system, methods, and devices are not limited bythe disclosure, but instead the scopes of the system, methods, ordevices are to be determined entirely by the claims.

While certain aspects of the system, methods, or devices are presentedbelow in certain claim forms, the inventor contemplates the variousaspects of the system, methods, or devices in any number of claim forms.Accordingly, the inventors reserve the right to add additional claimsafter filing the application to pursue such additional claim forms forother aspects of the system, methods, or devices.

EMBODIMENTS

Specific embodiments of the invention include the following:

-   1. A method of improving neural communication through the interface    between a first distinct region of tissue and a second distinct    region of tissue in the body of a person comprising administering    repetitive magnetic field pulses synchronously to both regions of    tissue.-   2. The method of Embodiment 1 wherein the magnetic pulses    administered to the first region of tissue and the second region of    tissue are generated by a single magnetic field source.-   3. The method of Embodiment 1 wherein the magnetic pulses    administered to the first region of tissue and the second region of    tissue are generated by more than one magnetic field source.-   4. The method of Embodiment 1 wherein the magnetic pulses are    generated by a coil or a moving permanent magnet.-   5. The method of Embodiment 1 wherein the magnetic pulse frequency    is fixed at or near a target frequency.-   6. The method of Embodiment 1 wherein the magnetic pulse frequency    hops periodically about an average target frequency.-   7. The method of Embodiment 5 or 6 wherein the magnetic pulse target    frequency is from about 1 Hz to about 10 Hz.-   8. The method of Embodiment 5 or 6 wherein the magnetic pulse target    frequency is from about 10 Hz to about 30 Hz.-   9. The method of Embodiment 1 wherein the strength of the magnetic    pulses is from about 10 Gauss to about 4 Tesla.-   10. The method of Embodiment 1 wherein the strength of the magnetic    pulses is adjusted based on the tolerance of the patient.-   11. A method of improving neural communication between a first    region of tissue and a second region of tissue in the body of a    person comprising administering alternating electric currents    synchronously to both regions of tissue.-   12. The method of Embodiment 11 wherein the electric currents    administered to the first region of tissue and the second region of    tissue are generated by a single electric current source, where    electric current flows through the interface between the regions.-   13. The method of Embodiment 11 wherein the electric currents    administered to the first region of tissue and the second region of    tissue are generated by more than one electric current source that    stimulates the two regions concurrently.-   14. The method of Embodiment 11 wherein the electric current    frequency is fixed at or near a target frequency.-   15. The method of Embodiment 11 wherein the electric current    frequency hops periodically about an average target frequency.-   16. The method of Embodiment 14 or 15 wherein the electric current    target frequency is from about 1 Hz to about 10 Hz.-   17. The method of Embodiment 14 or 15 wherein the electric current    target frequency is from about 10 Hz to about 30 Hz.-   18. The method of Embodiment 1 or 11 wherein the first region of    tissue is engineered and the second region of tissue is endogenous.-   19. The method of Embodiment 1 or 11 wherein the first region of    tissue is transplanted and the second region of tissue is    endogenous.-   20. The method of Embodiment 1 or 11 wherein the first region of    tissue is generated from stem cell injections and the second region    of tissue is endogenous.-   21. The method of Embodiment 1 or 11 wherein the first or second    region of tissue comprises muscle tissue.-   22. The method of Embodiment 1 or 11 wherein the first or second    region of tissue comprises brain tissue.-   23. The method of Embodiment 1 or 11 wherein the first or second    region of tissue comprises skin tissue.

While embodiments of the present invention have been shown and describedherein, it will be obvious to those skilled in the art that suchembodiments are provided by way of example only. Numerous variations,changes, and substitutions will now occur to those skilled in the artwithout departing from the invention. It should be understood thatvarious alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

EXAMPLES

The invention is described in greater detail by the followingnon-limiting examples.

Example 1

An 87-year-old female patient with moderate Alzheimer's disease,presented with a Mini-Mental State Examination (MMSE) score of 0, withsevere deficits in memory, cognition, speech aphasia, and motorcatatonia. The patient was administered stem cells via IV one year priorto therapy, with no improvement in symptoms. Experts believed that stemcells had entered regions of the brain and were viable, butcommunication had not been established.

Transcranial magnetic pulses were administered over the frontal lobe atapproximately 10 Hz, placed so that pulses would synchronously stimulateboth the stem cell tissue and existing tissue. 6 second pulse trainswere used, with 54 second inter-train interval for 30 trains.

Communication between implanted stem cell tissue and existing tissue wasgreatly improved, based on EEG data. Following 2 weeks of stimulation,her MMSE score increased to 5, catatonia was reduced by 30%, and thepatient began speaking in full sentences.

Example 2

An 8-year-old male patient had left side cerebrovascular injury due to atraffic accident. The patient had normal developmental history, butafter the accident, he presented with speech aphasia, general fine motorloss, loss of function of the left leg, and had slowed cognitivecomprehension. The patient had been administered stem cells via IV onemonth prior to therapy, with no improvement in symptoms. Expertsbelieved that stem cells had entered regions of the brain and wereviable, but communication had not been established.

Transcranial magnetic pulses were administered over the left motorcortex and frontal lobe at approximately 10 Hz, placed so that pulseswould synchronously stimulate both the stem cell tissue and existingtissue. 8 second pulse trains were used, with 52 second inter-trainintervals for 40 trains. After 2 months of therapy, general fine motorfunction improved by 30%. The patient was capable of sticking out histongue, began making ‘p’ sounds, recovered facial expressions, andimproved cognitive processing speed.

What is claimed is:
 1. A method of improving the symptoms of anAlzheimer's disease patient which comprises administering to the patientover the patient's frontal lobe repetitive magnetic field pulses at amagnetic pulse frequency that changes periodically about an averagetarget frequency that is 30 Hz or less.
 2. The method of claim 1 whereinthe symptoms that are improved include or more of the following: a.improved EEG profile b. improved Mini-Mental State Examination (MMSE)score c. reduction in catatonia d. improved memory e. improved speechand f. improved cognition.
 3. The method of claim 2 wherein the patientis pre-treated with a stem cell therapy.
 4. The method of claim 3wherein a strength of the magnetic pulses is from about 10 Gauss toabout 4 Tesla.
 5. The method of claim 4 wherein a strength of themagnetic pulses is adjusted based on a tolerance of a patient.
 6. Amethod of improving the symptoms of a patient who has experienced acerebrovascular injury which comprises administering to the patientadjacent to the patient's cerebrovascular injury repetitive magneticfield pulses at a magnetic pulse frequency that changes periodicallyabout an average target frequency that is 30 Hz or less.
 7. The methodof claim 6 wherein the symptoms that are improved include one or more ofthe following: a. improved EEG profile b. improved fine motor functionc. reduction in catatonia d. improved memory e. improved speech and f.improved cognition.
 8. The method of claim 7 wherein the patient ispre-treated with a stem cell therapy.
 9. The method of claim 8 wherein astrength of the magnetic pulses is from about 10 Gauss to about 4 Tesla.10. The method of claim 9 wherein a strength of the magnetic pulses isadjusted based on a tolerance of a patient.
 11. A method of improvingthe symptoms of an Alzheimer's disease patient which comprisesadministering to the patient over the patient's frontal lobe repetitivealternating currents generated by a current source at an electriccurrent frequency that changes periodically about an average targetfrequency that is 30 Hz or less.
 12. The method of claim 11 wherein thesymptoms that are improved include one or more of the following: a.improved EEG profile b. improved Mini-Mental State Examination (MMSE)score c. reduction in catatonia d. improved memory e. improved speechand f. improved cognition.
 13. The method of claim 12 wherein thepatient is pre-treated with a stem cell therapy.
 14. The method of claim13 wherein a strength of the electric current is adjusted based on atolerance of a patient.
 15. The method of claim 14 wherein the electriccurrent is delivered transcutaneously or subcutaneously.
 16. The methodof claim 15 wherein electrodes placed on the skin above the patient'sfrontal lobe are employed to deliver the transcutaneous electriccurrent.
 17. The method of claim 15 wherein a needle electrode or animplanted electrode array near the frontal lobe are employed to deliverthe subcutaneous electric current.
 18. A method of improving thesymptoms of a patient who has experienced a cerebrovascular injury whichcomprises administering to the patient adjacent to the patient'scerebrovascular injury alternating currents generated by a currentsource at an electric current frequency that changes periodically aboutan average target frequency that is 30 Hz or less.
 19. The method ofclaim 18 wherein the symptoms that are improved include one or more ofthe following: a. improved EEG profile b. improved fine motor functionc. reduction in catatonia d. improved memory e. improved speech and f.improved cognition.
 20. The method of claim 19 wherein the patient ispre-treated with a stem cell therapy.
 21. The method of claim 20 whereina strength of the electric current is adjusted based on a tolerance of apatient.
 22. The method of claim 21 wherein the electric current isdelivered transcutaneously or subcutaneously.
 23. The method of claim 22wherein electrodes placed on the skin above the patient'scerebrovascular injury are employed to deliver the transcutaneouselectric current.
 24. The method of claim 22 wherein a needle electrodeor an implanted electrode array near the cerebrovascular injury areemployed to deliver the subcutaneous electric current.
 25. A method ofregenerating nerves in a patient between a first distinct healthy regionof tissue and a second distinct compromised region of tissue in the bodyof a patient comprising administering repetitive magnetic field pulsessynchronously to both regions of tissue at a magnetic pulse frequencythat changes periodically about an average target frequency of about 30Hz or less whereby nerve regeneration is induced to connect the firsthealthy region of tissue with the second compromised region of tissue.26. The method of claim 25 wherein the patient is pre-treated with astem cell therapy.
 27. The method of claim 25 wherein the regenerationof nerves comprises an axonal growth into a nerve graft or into a distalend of a severed nerve.
 28. The method of claim 27 wherein theregeneration of nerves comprises an axonal growth into a nerve graft orinto a distal end of a severed nerve.